Topical antimicrobial agents

ABSTRACT

A method to inhibit microbial growth is provided comprising topically administering to a mammal afflicted with a pathology associated with microbial growth, such as a dermatological condition, an effective amount of a linear (C12-C22) 3-alken-2-one or 3, omega -alkadien-2-one.

This is a division of application Ser. No. 8/408,913 filed Mar. 22,1995.

BACKGROUND OF THE INVENTION

The odorous compounds of plants are volatile and are usually separatedfrom the plant material by steam distillation. They are known as thevolatile or essential oils, and consist of hydrocarbons, alcohols,ethers aldehydes and ketones: In the evaluations of conifers and in theoils from citrus fruits and from eucalyptus trees, alicyclichydrocarbons of the composition C₁₀ H₁₆ were found to be especiallyabundant, and it is to these compounds that the term "terpene" wasapplied in the restricted sense. It soon became evident, however, thatcompounds containing 15, 20, 30 and 40 carbon atoms also are closelyrelated to terpenes, and the term "terpene" in its broadest sense nowincludes all such compounds, which comprise repeating iso-C₅ units.

Many of the essential oils are employed in various flavors andfragrances, and their medicinal or biocidal potential has been thesubject of continued investigation. For example, the cyclic terpenones,α-ionone and β-ionone, were reported to exhibit moderate antibacterialactivity against S. mutans by I. Kubo et al., J. Agric. Food Chem., 41,2447 (1993). This bacterium is responsible for causing dental caries.Carvone, the chief component of spearmint oil, was reported to exhibitantifungal activity by V. Moleyar et al., Food Microbiol., 3, 331(1986). Kubo et al., J. Natural Products, 57, 9 (1994) subsequentlyreported that a number of cyclic and acyclic terpene alcohols, includinggeranylacetol, farnesol and farnesyl acetol, exhibited activity againstPr. acnes, the bacterium responsible for acne. However, the linearketone derived from farnesylacetol, farnesylacetone, was found to beinactive.

While some of these natural products may be potent enough for practicaluse, the synthesis or extraction of highly branched cyclic or alicyclicterpenes can be complex. Furthermore, terpenes such as ionone, acomponent of cedar oil, can cause allergic skin reactions. Nonetheless,essential oils and other phytochemicals are by definition biodegradableand renewable. Therefore, a continuing need exists for compounds ofnatural origin which exhibit useful levels of biocidal activity.

SUMMARY OF THE INVENTION

The present invention provides a method to inhibit the growth ofmicroorganisms, particularly microorganisms that are responsible formammalian skin pathologies, comprising contacting the microorganismswith an effective growth-inhibiting amount of a 3-alken-2-one of thegeneral formula (I): ##STR1## wherein n is 6-16 and X═Y═H or X and Ytogether are a covalent bond. Preferably n is 5-11 and X═Y═H, or n is6-10 and X and Y together are a covalent bond. Preferably the 3,4-doublebond is in the E- or trans-configuration.

Thus, the present invention also provides a composition adapted fortopical application to the skin comprising an effective antimicrobialamount of at least one compound of formula (I), in combination with adermatologically acceptable carrier. Preferred compositions in accordwith the present application are therapeutic compositions adapted fortopical application, as to the skin of a mammal afflicted with, or atrisk of affliction with, a pathology associated with a microorganismsuch as a bacterium, a yeast or a fungus. Novel compounds of formula (I)are also within the scope of the invention, including 3-hexadecen-2one.

The term "skin" as used herein is to be construed broadly, to includethe epidermis, the lips, the scalp, the epithelium of the eye, thesurfaces of body cavities, including the mouth, ear, nose, vagina, anusand the like, and the surfaces of wounds or lesions in the skin. Theterm "antimicrobial" or "inhibit," as used with respect to the growth ofmicroorganisms, is defined to encompass both complete inhibition(killing) of the microbes, as well as significant inhibition in growthor sporulation, as determined by the assays described herein, or byother standard assays, such as those disclosed by A. M. Janssen et al.,Planta medica, 53, 395 (1987). Thus, the term "antimicrobial"encompasses the use of the present compounds in deodorant compositions,to control body odor, as well as in therapeutic compositions. Allpercentages are by weight unless otherwise noted.

DETAILED DESCRIPTION OF THE INVENTION

A. Preparation

The 3-alken-2-ones of the present invention which are not commerciallyavailable, or which are novel compounds can be prepared by a number ofmethods available to the art. For example, 3-alken-2-ones of generalformula RCH═CH--C(O)CH₃ can generally be prepared by the crossed aldolcondensation of acetone and the alkanal (RCHO), followed by theacid-catalyzed elimination of water from the resultant hydroxy ketone.See, for example, B. V. Burger et al., J. Chem. Ecol., 16, 397 (1990)(3-dodec-2-one) and G. Tishenko et al., J. Gen. Chem. USSR, 33, 134(1963) (3-nonen-2-one). Alternatively, they can be prepared by theWittig or Wittig-Horner reaction.

Y.-Z. Huang et al., Synth. Commun., 19, 501 (1989) have also reported ageneral synthesis of 2-alken-2-ones (trans-RCH═CHC(O)CH₃) by thereaction of the aldehyde (RCHO) with α-bromoacetone in the presence oftri-n-butylstibine for 1-16 hr at 25°-50° C., and prepared compoundswherein R is n--C₄ H₉, n--C₈ H₁₇ or n--C₁₁ H₂₃. The 3-alken-2-onewherein R is n--C₁₃ H₂₆ has been reported by R. Kazlauskas et al., Aust.J. Chem., 33, 2097 (1980).

The 3-alkene-2-one wherein R is C₇ H₁₅ has been reported by H. A.Palma-Fleming et al., Phytochem., 22, 1503 (1983). The 3-aken-2-onewherein R is C₉ H₁₉, was prepared by A. A. Croteau et al., Tet. Letters,24, 2481 (1983), who report a general synthesis of E/Z mixtures of3-alken-2-ones by the condensation of lithiated α-silylketimine (Me₃Si--CHLi--C(═Nt--Bu)Me) with RCHO, followed by hydrolysis. Also, thepreparation of (Z)-3-alken-2-ones by the condensation of alkenyllithiocuprates with acetyl halides has been reported by N. Jabri et al.,Tetrahedron, 42, 1369 (1986). The preparation of 3-tetradecen-2-one(R═C₁₀ H₂₁) has been reported by J. Kang et al., Bull. Korean Chem.Soc., 15, 306 (1994).

B. Bioactivity

The present compounds and compositions comprising them can be employedin a wide range of antimicrobial applications, including surfacedisinfecting, and for treating foods such as fruits and seeds. Thepresent compounds are particularly useful to inhibit the growth ofpathological microorganisms, such as bacteria, fungi and yeasts on theskin of humans and of animals such as household pets, farm animals andzoo animals. Such gram-positive microorganisms include Propionibacteriumacnes which is the primary pathogen which causes human acne vulgaris,and the streptocci and staphylococci which cause impetigo. Mycoticinfections of animals and humans can also be treated, including tineacapitis, tinea cruris (jock itch), tinea corporis (ringworm), tineapedis (athlete's foot) and tinea unguium. Fungi associated with suchdermatophytosis include T. mentagrophytes, M. audevinii, T. rubrum, E.fioccosum, M. pelineum and Candida albicans.

The present compounds are also effective against fungi associated withinfections of the membranes of body cavities. Such infections includethrush, vaginitis and paronychia. See R. T. Yousef et al., Mykosen, 21,190 (1978) and H. Gershon, J. Pharm. Sci., 68, 82 (1979). The presentcompounds can also be used in cosmetic and skin-cleansing compositionssuch as soaps, shampoos, deodorants, and skin softening lotions, wherethey can function as deodorants, i.e., to control odor-causing bacteriaon the skin. The present compounds can also be employed in dentifrices,chewing gums, and mouthwashes to inhibit the growth of Streptococcusmutans, which is a causative agent for dental caries, and in shampoos,rinses, and other haircare products, to inhibit Pityrosporum ovale(dandruff, skin lesions in immune-suppressed subjects). Infections dueto Staphylococcus aureus are also susceptible to these compounds.

C. Compositions

Although in some instances, the present compounds may be administered inpure form, i.e., when they are liquids, it will generally be desirableto administer them to the skin as compositions or formulations, incombination with a dermatologically acceptable carrier, which may be asolid or a liquid.

Useful solid carriers include finely divided solids such as talc, clay,microcrystalline cellulose, silica, alumina and the like. Useful liquidcarriers include water, alcohols or glycols or water-alcohol/glycolblends, in which the present compounds can be dissolved or dispersed ateffective levels, optionally with the aid of non-toxic surfactants.Adjuvants such as flavorings, fragrances and additional antimicrobialagents can be added to optimize the properties for a given use. Theresultant liquid compositions can be applied from absorbent pads, usedto impregnate bandages and other dressings, or sprayed onto the affectedarea using pump-type or aerosol sprayers. The liquid compositions canalso be employed as eyedrops, mouth washes, douches, etc. Antibacterialpresaturated wipes are disclosed by Anderson (U.S. Pat. No. 4,896,768).

Thickeners such as synthetic polymers, fatty acids, fatty acid salts andesters, fatty alcohols, modified celluloses or modified mineralmaterials can also be employed with liquid carriers to form spreadablepastes, gels, ointments, soaps, and the like, for application directlyto the skin of the user.

The total concentration of one or more compounds of formula (I) in thepresent compositions can be varied widely, and will depend on factorssuch as the compatibility of the active ingredient(s) with the vehicle,the potency of the active ingredient(s) and the condition to be treated.Generally, the concentration of the compound(s) of formula (i) in aliquid composition, such as a lotion, will be from about 0.1-25 wt-%,preferably from about 0.5-10 wt-%. The concentration in a semi-solid orsolid composition such as a gel or a powder will be about 0.1-5 wt-%,preferably about 0.5-2.5 wt-%.

The present compounds of formula (I) are particularly useful to treathuman or animal acne by topical application, as gels, ointments,lotions, soaps, and the like. For a further discussion of the pathologyand etiology of acne, and of the formulation of aqueous cream and gelvehicles as carriers for other agents used to treat acne, see Klein etal. (U.S. Pat. No. 4,692,329). The total dosage delivered will depend onthe extent of the infected area to be treated, the severity of theinfection and the number of applications, as determined by the subject'sdermatologist, physician or veterinarian.

The present invention will be further described by reference to thefollowing detailed examples.

EXAMPLE 1 Synthesis of (E)-3-Alken-2-ones and(E)-3,13-Tetradecadien-2-one

To 5.0 g of piperidine, 5.0 g of glacial acetic acid and 250 mL ofacetone at reflux in a 500 mL round-bottomed flask was added 0.10 moleof one of the following aldehydes (octanal, nonanal, decanal, undecanal,10-undecenal, dodecanal, tridecanal, or tetradecanal) in 50 mL ofacetone dropwise over 0.5 hours. After addition, the solution wasrefluxed for an additional 5 hours. The acetone was removed in vacuo andthe residue was placed in 50 mL of diethyl ether. The ether solution waswashed with 2×50 mL water, 2×50 mL 1 M HCl and 2×50 mL saturated NaHCO₃.The ether solution was dried with anhydrous CaCl₂ and the ether wasremoved in vacuo. A pure sample of each compound was obtained bypreparative gas chromatography.

EXAMPLE 2 Spectral Data for (E)-3-Alken-2-ones and(E)-3,13Tetradecadien-2-one

Mass spectra of the following compounds were recorded on aHewlett-Packard gas chromatograph (Model 5890) fitted with a massselective detector (Model 5970) using a 12 m cross-linked methylsilicone capillary column. The gas chromatograph was programmed so theoven temperature was kept at 40° C. for 4 minutes, then increased to afinal temperature of 250° C. at a rate of 30° C./min and kept at thistemperature for four minutes. Mass spectral fragments below m/z=35 werenot recorded. The mass selective detector was tuned usingperfluorotributylamine and the internal computer tuning program.

The ¹ H and ¹³ C NMR spectra of the compounds were recorded at 300 MHzand 75 MHz respectively on Bruker QE plus. Samples were dissolved inCDCl₃, and chemical shifts are given in ppm relative totetramethylsilane (TMS) at zero ppm using the solvent peak a 77.0 ppm asthe internal standard. The synthetic 3-alken-2-ones and3,13-tetradecadien-2-one were shown to be the (E)-isomer by the ¹ H-NMRcoupling constant of 15.9 Hz for the olefinic protons.

A. (E)-3-Undecen-2-one (1)

300 MHz ¹ H-NMR (CDCl₃) δ=6.78(dt, 1H, J=15.9 Hz, 6.9 Hz), 6.03(dt, 1H,J=15.9 Hz, J=1.48 Hz), 2.21(s, 3H), 2.19(quart, 2H), 1.44(m, 2H),1.26(m, 8H) and 0.85(t, 3H); 75 MHz ¹³ C-NMR (CDCl₃) δ=198.74, 148.68,131.29, 32.50, 31.75, 29.17, 29.08, 28.12, 26.82 22.65, 14.09; and El-MSm/z=97(7), 83(5), 81(6), 71(15), 69(18),68(6), 55(50), 43(100), 41(40)and 39(19).

B. (E)-3-Dodecen-2-one (2)

300 MHz ¹ H-NMR (CDCl₃) δ=6.73(dt, 1H, J=15.9 Hz, 6.9 Hz), 5.99(dt, 1H,J=15.9 Hz, J=1.48 Hz), 2.18(s, 3H,) 2.15(quart, 2H), 1.38(m, 2H),1.21(m, 10H) and 0.81(t, 3H); 75 MHz ¹³ C-NMR (CDCl₃) δ=198.80, 148.72,131.31, 32.53, 31.87, 29.39, 29.23, 28.13, 26.84, 22.69 and 14.13; andEl-MS m/z=97(15), 83(11), 82(9), 81(8), 71(25), 69(18), 55(50), 43(100),41(37) and 36(18).

C. (E)-3-Tridecen-2-one (3)

300 MHz 1¹ H-NMR (CDCl₃) δ=6.81(dt, 1 H, J=15.9 Hz, 6.9 Hz), 6.06(dt,1H, J=15.9 Hz, J=1.48 Hz), 2.24(s, 3H) 2.22(quart. 2H), 1.46(m, 2H),1.26(m, 12H) and 0.88(t, 3H); 75 MHz ¹³ C-NMR (CDCl₃) δ=198.80, 148.69,131.24, 32.47, 31.85, 29.46, 29.37, 29.27, 29.17 28.07, 26.79, 22.65 and14.09; El-MS m/z=96(M⁺, 2), 181(8), 97(31), 96(14), 83(22), 81(20),71(34), 69(31), 55(65), 43(100), 41(44); and FT-IR (neat) 2925 2854,1700, 1677, 1628, 1467, 1360, 1253, 1189 and 980 cm⁻¹.

D. (E)-3-Tetradecen-2-one (4)

300 MHz H-NMR (CDCl₃) δ=6.79(dt, 1H, J=15.9 Hz, 6.9 Hz), 6.05(dt, 1H,J=15.9 Hz, J=1.48 Hz), 2.23(s, 3H), 2.21(quart, 2H), 1.45(m, 2H),1.26(m, 14H) and 0.87(t, 3H); 75 MHz ¹³ C-NMR (CDCl₃) δ=198.79, 148.71,131.31, 32.53, 31.94, 29.62, 29.57, 29.43, 29.36 29.23, 28.13, 26.84,22.72 and 14.15; El-MS m/z=97(21), 84(9), 83(8), 81(12), 71(30), 69(18),55(50), 43(100), 41(50) and 39(18).

E. (E)-3, 13-Tetradecadien-2-one (5)

300 MHz ¹ H-NMR (CDCl₃) δ=6.80(dt, 1H, J=15.9 Hz, 6.9 Hz), 6.06(dt, 1H,J=15.9 Hz, J=1.48 Hz), 5.80(m, 1H), 4.95(m, 2H), 2.24(s, 3H),2.22(quart, 2H), 2.03(quart, 2H), 1.46(m, 2H) and 1.28(m, 10H); 75 MHz¹³ C-NMR (CDCl₃) δ=198.83, 148.71, 139.18, 131.32 114.20, 33.83, 32.52,29.38, 29.21, 29.12, 28.94, 28.13, 26.87; El-MS m/z=97(20), 95(14),81(21), 71(19), 69(17), 67(23), 55(59), 43(100), 41(71) and 39(35).

F (E)-3-Pentadecen-2-one (6).

300 MHz ¹ H-NMR (CDCl₃) δ=6.80(dt, 1H, J=15.9 Hz, 6.9 Hz), 6.05(dt, 1H,J=15.9 Hz, J=1.48 Hz), 2.23(s, 3H), 2.21(quart, 2H), 1.46(m, 2H),1.26(m, 16H) and 0.88(t, 3H); 75 MHz ¹³ C-NMR (CDCl₃) δ=198.79, 148.71,131.31, 32.53, 31.96, 29.66, 29.57, 29.44, 29.38 29.33, 29.24, 28.14,26.85, 22.73 and 14.16; El-MS m/z=97(18), 84(10), 81(11), 71(28),69(16), 68(10), 67(10), 55(46), 43(100), and 41(40)

G. (E)-3-Hexadecen-2-one (7)

300 MHz ¹ H-NMR (CDCl₃) δ=6.80(dt, 1H, J=15.9 Hz, 6.9 Hz), 6.06(dt, 1H,J=15.9 Hz, J=1.48 Hz), 2.24(s, 3H), 2.22(quart, 2H), 1.47(m, 2H).1.26(m, 18H) and 0.88(t, 3H); 75 MHz ¹³ C-NMR (CDCl₃) δ=198.83, 148.74,131.31, 32.54, 31.97, 29.71, 29.68, 29.58, 29.54 29.44, 29.41, 29.25,28.15, 26.85, 22.74 and 14.17; El-MS m/z=97(18), 84(8), 83(8), 82(8),81(9), 71(30), 69(15), 55(42), 43(100), and 41(50).

H. (E)-3-Heptadecen-2-one (8)

300 MHz ¹ H-NMR (CDCl₃) δ=6.80(dt, 1H, J=15.9 Hz, 6.9 Hz), 6.07(dt, 1H,J=15.9 Hz, J=1.48 Hz), 2.24(s, 3H), 2.22(quart, 2H), 1.47(m, 2H),1.26(m, 20H) and 0.88(t, 3H); 75 MHz ¹³ C-NMR (CDCl₃) δ=198.83, 148.74,131.32, 32.54, 31.97, 29.70, 29.58, 29.44, 29.41 29.34, 29.25, 28.15,26.87, 22.74 and 14.18; and El-MS m/z=252(M+, 3), 97(19), 84(8), 83(10),81(11), 71(28), 69(14), 55(39), 43(100) and 41(50).

EXAMPLE 3 Bioassays

The microorganisms tested were from the American Type Culture Collection(Rockville, Md.). They are Bacillus subtilis ATCC 9372 Brevibacteriumammoniagenes ATCC 6872, Staphylococcus aureus ATCC 12598, Streptococusmutans ATCC 25175, Propionibacterium acnes ATCC 11827, Pseudimonasaeruginosa ATCC 10145, Enterobacter aerogenes ATCC 13048, Eschericiacoli ATCC 9637, Proteus vulgaris ATCC 133315, Saccharomyces cerevisiaeATCC 7754, Candida utilis ATCC 9226, Pityrosporum ovale ATCC 14521,Penicillium chrysogenum ATCC 10106 and Trichophyton mentagrophytes ATCC18748.

The bacterial culture media except for S. mutans was 0.8% nutrient broth(BBL), 0.5% yeast Extract (Difco) and 0.1% glucose (NYG broth). S.mutans was cultured in 3.7% brain heart infusion broth (Difco). Allfungi, except P. ovale and T. mentagrophytes were cultured in a 2.5%malt extract broth (BBL). P. ovale was cultured in 1% bactopeptone(Difco), 0.5% yeast extract, 1% glucose and 0.1% corn oil. For T.mentagrophytes the culture media was 1% bactopeptone and 4% glucose.

Freeze dried samples were prepared for testing as follows. B. subtilis,S. cerevisiae, C utilis, and P. ovale, were shake-cultured for two daysat 30° C. P. chysogenum and T. mentagrophytes were shake-cultured for 5days at 30° C. B. ammoniagenes and E. aerogenes were stationarilycultured at 30° C. S. aureus S. mutans, P. acnes, P. aeruginosa, E. coliand P. vulgaris were stationarily cultured at 37° C.

The minimum inhibitory concentration (MIC) of the 3-alken-2-ones(compounds 1-4, 6-8) and 3,13-tetradecadien-2-one (compound 5) wasperformed using a two-fold serial broth dilution. Each test compound wasdissolved in DMF and 30 μL of this sample was dissolved in 3 mL of theapplicable medium. A 30 μL sample of the previously described culture ofeach microorganism was added to the various medium solutions. After twodays, the cultures of B. subtilis, S. cerevisiae, C utilis, B.ammoniagenes, E. aerogenes, S. aureus, S. mutans, P. acnes, P.aeruginosa, E. coli and P. vulgaris were examined for turbidity (OD at660 nm). The fungi, P. ovale, P. chysogenum and T. mentagrophytes, wereexamined visually for growth at 3 days (P. ovale) and 5 days (P.chrysogeum and T. meuagrophytes). The MIC was determined as the lowestconcentration for each compound that no growth was observed. The highestconcentration used in these tests was 800 μg/mL.

                                      TABLE 1                                     __________________________________________________________________________    MIC of (E)-3-Alken-2-ones and (E)-3,13-tetradecadien-2-one                    (μg/mL)                                                                    Organism            1    2    3   4   5   6   7   8                           __________________________________________________________________________    Bacillus subtilis ATCC 9372                                                                       100  100  100 >800                                                                              >800                                                                              >800                                                                              >800                                                                              >800                        Brevibacterium ammoniagenes ATCC 6872                                                             200  100  100 >800                                                                              >800                                                                              >800                                                                              >800                                                                              >800                        Staphylococcus aureus ATCC 12598                                                                  200  100  50  >800                                                                              >800                                                                              >800                                                                              >800                                                                              >800                        Streptococus mutans ATCC 25175                                                                    100   50  25  25  25  200 400 800                         Propionibacterium acnes ATCC 11827                                                                 50   25  12.5                                                                              12.5                                                                              12.5                                                                              6.25                                                                              3.13                                                                              3.13                        Pseudimonas aeruginosa ATCC 10145                                                                 >800 >800 >800                                                                              >800                                                                              >800                                                                              >800                                                                              >800                                                                              >800                        Enterobacter aerogenes ATCC 13048                                                                 >800 >800 >800                                                                              >800                                                                              >800                                                                              >800                                                                              >800                                                                              >800                        Eschericia coli ATCC 9637                                                                         >800 >800 >800                                                                              >800                                                                              >800                                                                              >800                                                                              >800                                                                              >800                        Proteus vulgaris ATCC 133315                                                                       50   50  800 >800                                                                              >800                                                                              >800                                                                              >800                                                                              >800                        Saccharomyces cerevisiae ATCC 7754                                                                800  800  >800                                                                              >800                                                                              >800                                                                              >800                                                                              >800                                                                              >800                        Candia utilis ATCC 9226                                                                            50  400  >800                                                                              >800                                                                              >800                                                                              >800                                                                              >800                                                                              >800                        Pityrosporum ovale ATCC 14521                                                                     100  100  100 100 200 400 >800                                                                              >800                        Penicillium chrysogenum ATCC 10106                                                                100  100  800 800 800 >800                                                                              >800                                                                              >800                        Trichophyton mentagrophytes ATCC18748                                                             100  100  25  12.5                                                                              12.5                                                                              800 >800                                                                              >800                        __________________________________________________________________________

As demonstrated by the data summarized in Table 1 the greatest activityobserved with compounds 1-8 occurred against P. aches, the primarypathogen responsible for causing human acne. Compounds 1-5 alsoexhibited substantial activity against T. mentagrophytes, the causativeagent of athlete's foot and compounds 1-7 inhibited Streptococcus mutans(dental caries). Compounds 1-6 also exhibited somewhat lesser activityagainst P. ovale (dandruff) and compounds (1)-(3) were active against S.aureus and Proteus vulgaris. Specifically, (E)-3-tridecen-2-one (3),showed activity against all of the gram-positive bacteria (B. subtilis,B. ammoniagenes, S. aureus, S. mutans, and P. acnes) in the test. It wasmost active against P. acnes, having a minimum inhibitory concentration(MIC) of 12.5 μg/mL. This compound was not active against thegram-negative bacteria, P. aeruginosa, E. aerogenes and E. coli.Activity against yeast was mixed, no activity was seen against S.cerevisiae and C utilis, although P. ovale showed moderate inhibition.Weak activity was seen with fungi P. chysogenum, while the fungi T.mentagrophytes had a MIC of 25 μg/mL.

(E)-3-tetradecen-2-one (4), showed activity against some gram-positivebacteria (S. mutans, and P. acnes) in the test. It was most active withP. acnes having a minimum inhibitory concentration (MIC) of 12.5 μg/mL.This compound was not active against the gram-negative bacteria, P.aeruginosa, E. aerogenes and E. coli. Activity against yeast was mixed,no activity was seen against S. cerevisiae and C. utilis, although P.ovale showed moderate inhibition. Weak activity was seen with fungi P.chrysogenum, while the fungi T. mentagrophytes had a MIC of 12.5 μg/mL.

The synthetic products, (E)-3-hexadecen-2-one (7) and(E)-3-heptadecen-2-one (8), were inactive to all of the bacteria andfungi in the test, except S. mutans and P. acnes. With S. mutans (7) wasweakly active, but (7) and (8) exhibited strong activity (3.13 μg/mL)against P. acnes.

EXAMPLE 4

A powder composition may be prepared having the following formulation:

    ______________________________________                                                          Per Canister                                                ______________________________________                                        Compound 4          1.0    g                                                  Talc                99     g                                                  ______________________________________                                    

EXAMPLE 5

A lotion composition may be prepared having the following formulation:

    ______________________________________                                                           Per Canister                                               ______________________________________                                        Compound 7           1.0    g                                                 Cetyl Alcohol        25     g                                                 Glyceryl Stearate    25     g                                                 Glycerol             20     g                                                 Water                10     g                                                 Stearyl Alcohol      10     g                                                 ______________________________________                                    

EXAMPLE 6

A lotion composition may be prepared having the following formulation:

    ______________________________________                                                           Per Canister                                               ______________________________________                                        Compound 7           0.5    g                                                 Compound 4           0.5    g                                                 Cetyl Alcohol        25     g                                                 Glyceryl Stearate    25     g                                                 Glycerol             20     g                                                 Water                10     g                                                 Stearyl Alcohol      10     g                                                 ______________________________________                                    

Other examples of useful dermatological compositions which can be usedto deliver the compounds of claim 1 to the skin are disclosed in Jacquetet al. (U.S. Pat. No. 4,608,392), Geria (U.S. Pat. No. 4,992,478), Smithet al. (U.S. Pat. No. 4,559,157) and Wortzman (U.S. Pat. No. 4,820,508).

All publications and patents are incorporated by reference herein, asthough individually incorporated by reference. The invention has beendescribed with reference to various specific and preferred embodimentsand techniques. However, it should be understood that many variationsand modifications may be made while remaining within the spirit andscope of the invention.

What is claimed is:
 1. A method of treating acne comprising topicallyapplying to the skin of a human afflicted with acne a compositioncomprising an effective amount of a compound of formula (I): ##STR2##wherein n is 6-16 and X and Y are H or together are a colvalent bond; incombination with a dermatologically acceptable carrier.
 2. The method ofclaim 1 wherein X and Y are both H.
 3. The method of claim 1 wherein nis 5-11.
 4. The method of claim 1 wherein the carrier is a liquid andthe composition is a solution, a liquid dispersion or a gel.
 5. Themethod of claim 1 wherein the carrier is a solid and the composition isa powder.
 6. The method of claim 1 wherein the composition is a soap.